Delirium and frailty in older adults: Clinical overlap and biological underpinnings.

Frailty and delirium are two common geriatric syndromes sharing several clinical characteristics, risk factors, and negative outcomes. Understanding their interdependency is crucial to identify shared mechanisms and implement initiatives to reduce the associated burden. This literature review summarizes scientific evidence on the complex interplay between frailty and delirium; clinical, epidemiological, and pathophysiological commonalities; and current knowledge gaps. We conducted a PubMed systematic search in June 2023, which yielded 118 eligible articles out of 991. The synthesis of the results-carried out by content experts-highlights overlapping risk factors, clinical phenotypes, and outcomes and explores the influence of one syndrome on the onset of the other. Common pathophysiological mechanisms identified include inflammation, neurodegeneration, metabolic insufficiency, and vascular burden. The review suggests that frailty is a risk factor for delirium, with some support for delirium associated with accelerated frailty. The proposed unifying framework supports the integration and measurement of both constructs in research and clinical practice, identifying the geroscience approach as a potential avenue to develop strategies for both conditions. In conclusion, we suggest that frailty and delirium might be alternative-sometimes coexisting-manifestations of accelerated biological aging. Clinically, the concepts addressed in this review can help approach older adults with either frailty or delirium from a different perspective. From a research standpoint, longitudinal studies are needed to explore the hypothesis that specific pathways within the biology of aging may underlie the clinical manifestations of frailty and delirium. Such research will pave the way for future understanding of other geriatric syndromes as well.

Mapping 15-year depressive symptom transitions in late life: population-based cohort study.

BACKGROUND: The longitudinal course of late-life depression remains under-studied. AIMS: To describe transitions along the depression continuum in old age and to identify factors associated with specific transition patterns. METHOD: We analysed 15-year longitudinal data on 2745 dementia-free persons aged 60+ from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression (minor and major) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; subsyndromal depression (SSD) was operationalised as the presence of ≥2 symptoms without depression. Multistate survival models were used to map depression transitions, including death, and to examine the association of psychosocial (social network, connection and support), lifestyle (smoking, alcohol consumption and physical activity) and clinical (somatic disease count) factors with transition patterns. RESULTS: Over the follow-up, 19.1% had ≥1 transitions across depressive states, while 6.5% had ≥2. Each additional somatic disease was associated with a higher hazard of progression from no depression (No Dep) to SSD (hazard ratio 1.09; 1.07-1.10) and depression (Dep) (hazard ratio 1.06; 1.04-1.08), but also with a lower recovery (HRSSD-No Dep 0.95; 0.93-0.97 [where 'HR' refers to 'hazard ratio']; HRDep-No Dep 0.96; 0.93-0.99). Physical activity was associated with an increased hazard of recovery to no depression from SSD (hazard ratio 1.49; 1.28-1.73) and depression (hazard ratio 1.20; 1.00-1.44), while a richer social network was associated with both higher recovery from (HRSSD-No Dep 1.44; 1.26-1.66; HRDep-No Dep 1.51; 1.34-1.71) and lower progression hazards to a worse depressive state (HRNo Dep-SSD 0.81; 0.70-0.94; HRNo Dep-Dep 0.58; 0.46-0.73; HRSSD-Dep 0.66; 0.44-0.98). CONCLUSIONS: Older people may present with heterogeneous depressive trajectories. Targeting the accumulation of somatic diseases and enhancing social interactions may be appropriate for both depression prevention and burden reduction, while promoting physical activity may primarily benefit recovery from depressive disorders.

The body of evidence of late-life depression: the complex relationship between depressive symptoms, movement, dyspnea and cognition.

BACKGROUND: Physical symptoms play an important role in late-life depression and may contribute to residual symptomatology after antidepressant treatment. In this exploratory study, we examined the role of specific bodily dimensions including movement, respiratory functions, fear of falling, cognition, and physical weakness in older people with depression. METHODS: Clinically stable older patients with major depression within a Psychiatric Consultation-Liaison program for Primary Care underwent comprehensive assessment of depressive symptoms, instrumental movement analysis, dyspnea, weakness, activity limitations, cognitive function, and fear of falling. Network analysis was performed to explore the unique adjusted associations between clinical dimensions. RESULTS: Sadness was associated with worse turning and walking ability and movement transitions from walking to sitting, as well as with worse general cognitive abilities. Sadness was also connected with dyspnea, while neurovegetative depressive burden was connected with activity limitations. DISCUSSION: Limitations of motor and cognitive function, dyspnea, and weakness may contribute to the persistence of residual symptoms of late-life depression.

A tale of two constructs: combined assessment of demoralization and subjective incompetence.

Demoralization comprises multiple dimensions. Among them, Subjective Incompetence (SI) is the perception of being incapable of appropriate action in demanding circumstances. SI may be an early sign of demoralization preceding hopelessness, thus we aimed at integrating items related to Subjective Incompetence into the clinical assessment of demoralization. We assessed 414 subjects from the general population with the Demoralization Scale, 24 items (DS24) and the Subjective Incompetence Scale, 12 items (SIS12). We used multiple approaches to detect the optimal number of factors and their item structure, then conducted Bayesian Item Response Theory analyses to study item psychometric properties. Item Response Theory models were used to extrapolate latent severity ratings of clinical dimensions. We modelled the DS24 with five factors (Disheartenment, Sense of Failure, Helplessness, Irritability, Loss of Purpose) and the SIS12 with three (Subjective Incompetence, Inability to plan, Inability to Deal). The more complex IRT model had the best predictive value and helped to identify the items with better discrimination properties across the different dimensions. Twenty items were retained and used to develop the combined Demoralization and Subjective Incompetence Scale (DSIS20), which maintained high correlation with raw and latent trait scores of the longer versions. We combined selected items of the DS24 and the SIS12 to develop the DSIS20, a shorter assessment instrument that includes Subjective Incompetence as well as other clinical dimensions of demoralization. Further study may clarify if DSIS20 may be helpful for the early detection of demoralization.

Late-life depression and multimorbidity trajectories: the role of symptom complexity and severity.

INTRODUCTION: as late-life depression is associated with poor somatic health, we aimed to investigate the role of depression severity and symptom phenotypes in the progression of somatic multimorbidity. METHODS: we analysed data from 3,042 dementia-free individuals (60+) participating in the population-based Swedish National Study on Aging and Care in Kungsholmen. Using the baseline clinical assessment of 21 depressive symptoms from the Comprehensive Psychopathological Rating Scale, we: (i) diagnosed major, minor (in accordance with DSM-IV-TR) and subsyndromal depression; (ii) extracted symptom phenotypes by applying exploratory network graph analysis. Somatic multimorbidity was measured as the number of co-occurring chronic diseases over a 15-year follow-up. Linear mixed models were used to explore somatic multimorbidity trajectories in relation to baseline depression diagnoses and symptom phenotypes, while accounting for sociodemographic and behavioural factors. RESULTS: in multi-adjusted models, relative to individuals without depression, those with major (ß per year: 0.33, 95% confidence interval [CI]: 0.06-0.61) and subsyndromal depression (ß per year: 0.21, 95%CI: 0.12-0.30) experienced an accelerated rate of somatic multimorbidity accumulation, whereas those with minor depression did not. We identified affective, anxiety, cognitive, and psychomotor symptom phenotypes from the network analysis. When modelled separately, an increase in symptom score for each phenotype was associated with faster multimorbidity accumulation, although only the cognitive phenotype retained its association in a mutually adjusted model (ß per year: 0.07, 95%CI: 0.03-0.10). CONCLUSIONS: late-life major and subsyndromal depression are associated with accelerated somatic multimorbidity. Depressive symptoms characterised by a cognitive phenotype are linked to somatic health change in old age.

Risk Prediction Models for Depression in Community-Dwelling Older Adults.

OBJECTIVE: To develop streamlined Risk Prediction Models (Manto RPMs) for late-life depression. DESIGN: Prospective study. SETTING: The Survey of Health, Ageing and Retirement in Europe (SHARE) study. PARTICIPANTS: Participants were community residing adults aged 55 years or older. MEASUREMENTS: The outcome was presence of depression at a 2-year follow up evaluation. Risk factors were identified after a literature review of longitudinal studies. Separate RPMs were developed in the 29,116 participants who were not depressed at baseline and in the combined sample of 39,439 of non-depressed and depressed subjects. Models derived from the combined sample were used to develop a web-based risk calculator. RESULTS: The authors identified 129 predictors of late-life depression after reviewing 227 studies. In non-depressed participants at baseline, the RPMs based on regression and Least Absolute Shrinkage and Selection Operator (LASSO) penalty (34 and 58 predictors, respectively) and the RPM based on Artificial Neural Networks (124 predictors) had a similar performance (AUC: 0.730-0.743). In the combined depressed and non-depressed participants at baseline, the RPM based on neural networks (35 predictors; AUC: 0.807; 95% CI: 0.80-0.82) and the model based on linear regression and LASSO penalty (32 predictors; AUC: 0.81; 95% CI: 0.79-0.82) had satisfactory accuracy. CONCLUSIONS: The Manto RPMs can identify community-dwelling older individuals at risk for developing depression over 2 years. A web-based calculator based on the streamlined Manto model is freely available at https://manto.unife.it/ for use by individuals, clinicians, and policy makers and may be used to target prevention interventions at the individual and the population levels.

Country differences in the cross-sectional associations between smoking and depressive symptoms in adolescence.

BACKGROUND: The aim of the present study was to compare the cross-sectional association between smoking and depressive symptoms among adolescents between Sweden and Italy, two countries historically characterized by different norms about tobacco use and different tobacco control efforts. METHODS: A cross-sectional study including 3283 adolescents 15-16 years of age participating in the Swedish KUPOL study and 1947 same-age adolescents from the Italian BE-TEEN study. Current smoking was defined as any smoking in the past 30 days. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and the internalizing score of the Strengths and Difficulties Questionnaire (SDQ). Country differences were explored in stratified and interaction analyses. RESULTS: Current smoking was associated with a 2- to 3-fold increased odds of depressive symptoms among Swedish adolescents using both CES-DC and SDQ internalizing scale. Among Italian adolescents, slightly lower increased odds of 1.5-2.5 for depressive symptoms with smoking were found using the CES-DC but not the SDQ scale. Both multiplicative and additive interactions for country were significant. The association between smoking and depressive symptoms was weaker among Italian compared with Swedish adolescents for both scores. CONCLUSIONS: Countries with different tobacco norms and control show different associations between smoking and depressive symptoms in adolescence, probably due to different psychosocial profiles of smokers. These findings need to be considered when planning tobacco prevention programmes, e.g. by focusing on early detection of mental health distress among adolescents in settings with declining smoking prevalence and restrictive tobacco control environments.

Sleep disturbances and the speed of multimorbidity development in old age: results from a longitudinal population-based study.

BACKGROUND: Sleep disturbances are prevalent among older adults and are associated with various individual diseases. The aim of this study was to investigate whether sleep disturbances are associated with the speed of multimorbidity development among older adults. METHODS: Data were gathered from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based study of subjects aged 60+ (N = 3363). The study included a subsample (n = 1189) without multimorbidity at baseline (< 2 chronic diseases). Baseline sleep disturbances were derived from the Comprehensive Psychiatric Rating Scale and categorized as none, mild, and moderate-severe. The number of chronic conditions throughout the 9-year follow-up was obtained from clinical examinations. Linear mixed models were used to study the association between sleep disturbances and the speed of chronic disease accumulation, adjusting for sex, age, education, physical activity, smoking, alcohol consumption, depression, pain, and psychotropic drug use. We repeated the analyses including only cardiovascular, neuropsychiatric, or musculoskeletal diseases as the outcome. RESULTS: Moderate-severe sleep disturbances were associated with a higher speed of chronic disease accumulation (ß/year = 0.142, p = 0.008), regardless of potential confounders. Significant positive associations were also found between moderate-severe sleep disturbances and neuropsychiatric (ß/year = 0.041, p = 0.016) and musculoskeletal (ß/year = 0.038, p = 0.025) disease accumulation, but not with cardiovascular diseases. Results remained stable when participants with baseline dementia, cognitive impairment, or depression were excluded. CONCLUSION: The finding that sleep disturbances are associated with faster chronic disease accumulation points towards the importance of early detection and treatment of sleep disturbances as a possible strategy to reduce chronic multimorbidity among older adults.

Physical exercise for late life depression: effects on cognition and disability.

BACKGROUND: Late-life depression is often associated with cognitive impairments and disability, which may persist even after adequate antidepressant drug treatment. Physical exercise is increasingly recognized as an effective antidepressant agent, and may exert positive effects on these features too. However, few studies examined this issue, especially by comparing different types of exercises. METHODS: We performed secondary analyses on data from the Safety and Efficacy of Exercise for Depression in Seniors study, a trial comparing the antidepressant effectiveness of sertraline (S), sertraline plus thrice-weekly non-progressive exercise (S+NPE), and sertraline plus thrice-weekly progressive aerobic exercise (S+PAE). Exercise was conducted in small groups and monitored by heart rate meters. Patients with late-life depression without severe cognitive impairment were recruited from primary care and assessed at baseline and 24 weeks, using the Montreal Cognitive Assessment (MOCA, total and subdomain scores) and Brief Disability Questionnaire. Analyses were based on Generalized Linear Models. RESULTS: In total, 121 patients (mean age 75, 71% females) were randomized to the study interventions. Compared with the S group, patients in the S+PAE group displayed greater improvements of MOCA total scores (p=0.006, effect size=0.37), visuospatial/executive functions (p=0.001, effect size=0.13), and disability (p=0.02, effect size=-0.31). Participants in the S+NPE group did not display significant differences with the control group. CONCLUSIONS: Adding aerobic, progressive exercise to antidepressant drug treatment may offer significant advantages over standard treatment for cognitive abilities and disability. These findings suggest that even among older patients exercise may constitute a valid therapeutic measure to improve patients' outcomes.

Somatic disease burden and depression risk in late life: a community-based study.

AIMS: Co-occurring somatic diseases exhibit complex clinical profiles, which can differentially impact the development of late-life depression. Within a community-based cohort, we aimed to explore the association between somatic disease burden, both in terms of the number of diseases and their patterns, and the incidence of depression in older people. METHODS: We analysed longitudinal data of depression- and dementia-free individuals aged 60+ years from the population-based Swedish National Study on Aging and Care in Kungsholmen. Depression diagnoses were clinically ascertained following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision over a 15-year follow-up. Somatic disease burden was assessed at baseline through a comprehensive list of chronic diseases obtained by combining information from clinical examinations, medication reviews and national registers and operationalized as (i) disease count and (ii) patterns of co-occurring diseases from latent class analysis. The association of somatic disease burden with depression incidence was investigated using Cox models, accounting for sociodemographic, lifestyle and clinical factors. RESULTS: The analytical sample comprised 2904 people (mean age, 73.2 [standard deviation (SD), 10.5]; female, 63.1%). Over the follow-up (mean length, 9.6 years [SD, 4 years]), 225 depression cases were detected. Each additional disease was associated with the occurrence of any depression in a dose-response manner (hazard ratio [HR], 1.16; 95% confidence interval [CI]: 1.08, 1.24). As for disease patterns, individuals presenting with sensory/anaemia (HR, 1.91; 95% CI: 1.03, 3.53), thyroid/musculoskeletal (HR, 1.90; 95% CI: 1.06, 3.39) and cardiometabolic (HR, 2.77; 95% CI: 1.40, 5.46) patterns exhibited with higher depression hazards, compared to those without 2+ diseases (multimorbidity). In the subsample of multimorbid individuals (85%), only the cardiometabolic pattern remained associated with a higher depression hazard compared to the unspecific pattern (HR, 1.71; 95% CI: 1.02, 2.84). CONCLUSIONS: Both number and patterns of co-occurring somatic diseases are associated with an increased risk of late-life depression. Mental health should be closely monitored among older adults with high somatic burden, especially if affected by cardiometabolic multimorbidity.

Air pollution, social engagement, and depression in older adults: Results from a Swedish population-based cohort study.

Although emerging research has investigated the relationship between outdoor air pollution and depression risk in older adults, the results remain inconclusive. We aimed to determine the relationship between long-term exposure to ambient air pollution and depression among older adults and explore whether active social engagement may modify this association. At baseline (2001-2004), 2812 depression-free older adults from Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) were included. SNAC-K is a longitudinal population-based cohort in Stockholm, Sweden. Incident depression cases occurred during 2004-2013 were ascertained using the Diagnostic and Statistical Manual of Mental Disorders 4th Edition. Air pollution [particulate matter (PM) and nitrogen oxides (NOx)] at the residency were estimated using dispersion models. Social engagement was measured as active participation in social activities (at least twice/week) or inactive (less than twice/week) in the last 12 months. The hazard ratios (HR) and 95% confidence intervals of depression from air pollution exposure of 3-year moving average before diagnosis (1-µg/m3 difference in PM2.5 and PM10, and 10-µg/m3 difference in NOx) were obtained from Cox models considering greenspace and noise. A product term of air pollutant and social activity was added to test the multiplicative interaction and attributable proportion due to interaction was calculated for assessing additive interaction. We identified 137 (4.9%) incident depression cases. Participants exposed to higher concentrations of PM2.5, NOx, and PM10 had 53% (HR:1.53 [1.22, 1.93]), 26% (HR:1.26 [1.01, 1.58]), and 7% (HR:1.07 [0.98, 1.18]) increased hazard of depression, respectively. These associations were largely attenuated in people with active social engagement (HR for PM2.5: 1.04 [0.70, 1.55]; HR for PM10: 0.98 [0.81, 1.18]; and HR for NOx: 1.09 [0.71, 1.66]). Our findings suggest long-term exposure to air pollution may be a risk factor for depression among older adults. An active social engagement might however decrease this risk.

COVID-19 collateral damage-psychological burden and behavioural changes among older adults during the first outbreak in Stockholm, Sweden: a cross-sectional study.

OBJECTIVES: To explore the indirect negative effects of COVID-19 restrictions (collateral damage) on the lives and health of older adults living in central Stockholm, and to characterise the sociodemographic profile of those with the highest susceptibility to this damage. DESIGN: Cross-sectional study. SETTING: District of Kungsholmen in Stockholm, Sweden. PARTICIPANTS: Older adults aged 68 years and above (n=1231) who participated in the ad hoc COVID-19-related phone questionnaire administered by trained staff between May and June 2020 and who had previously attended the regular follow-up assessment of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) during 2016-2019. PRIMARY AND SECONDARY OUTCOME MEASURES: Three dimensions of collateral damage: psychological burden (feelings of worry, stress and loneliness), reductions in social and physical activities, and reductions in medical and social care use since the beginning of the pandemic. Logistic regression models were used to test the association between age, sex, education and living arrangement, and the risk of collateral damage. RESULTS: Vast majority of participants adhered to the national public health recommendations, with over three-quarters practising self-isolation (n=928). Half of the sample reported psychological burden, 55.3% reported reductions in social or physical activity, and 11.3% reported decreased medical or social care use. Over three quarters of participants (77.8%) were affected by at least one of the three collateral damage dimensions. Female sex was the strongest sociodemographic predictor of both individual and co-occurring dimensions of collateral damage. CONCLUSIONS: COVID-19 and its restrictions during the first half of 2020 had a negative effect on the health and lives of a majority of the elderly living in central Stockholm. Women were at a higher risk of these negative consequences. We emphasise the need for predefined, evidence-based interventions to support those who are most susceptible to these consequences, both during the pandemic and once the outbreak is overcome.

Pre-pandemic Physical Function and Social Network in Relation to COVID-19-Associated Depressive Burden in Older Adults in Sweden.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic, as well as the measures intended to limit its spread, have likely affected older adults' depressive burden. Good physical functioning and a rich social network may benefit older adults' mental health. We examined whether pre-pandemic physical functioning and social network were associated with depressive burden during the first wave of the COVID-19 pandemic in Stockholm, Sweden. Research Design and Methods: A telephone assessment of depressive burden using the symptoms of sadness, anxiety, worrying, reduced sleep, and reduced appetite was conducted in May-September 2020 in 930 older adults from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), an ongoing population-based study. Objective measures of gait speed, muscle strength, and balance; and self-reports of social connections and support were collected in 2016-2019. Logistic models were adjusted for sociodemographic, clinical, lifestyle, and pandemic-related factors (loneliness, change in physical and social engagement, and experience of death due to COVID-19). Results: Only good muscle strength (odds ratio [OR]: 0.53; 95% confidence interval [CI]: 0.32-0.85; ref: poor strength, ≥17 s) and rich social support (OR: 0.67; 95% CI: 0.45-0.99; ref: poor support) exhibited an independent association with depressive burden, even after accounting for pandemic-related factors. A combination of good muscle strength and rich social support were associated with the greatest reduction in depressive burden (OR: 0.35; 95% CI: 0.18-0.66; ref: poor social support and poor muscle strength). Discussion and Implications: Prepandemic social support and muscle strength could supply older adults with resilience against the depressive burden associated with the COVID-19 pandemic.

Factors associated with physical activity reduction in Swedish older adults during the first COVID-19 outbreak: a longitudinal population-based study.

BACKGROUND: Physical activity (PA) decreased during the COVID-19 pandemic, especially among older adults, potentially leading to adverse consequences for their health. However, factors associated with reductions of PA during the pandemic have not been examined in a population-based sample of older adults. Thus, the aim of this study was to explore the association of pre-pandemic physical, mental, social and lifestyle factors with reductions in PA in older adults during the first wave of COVID-19, and whether the associations differed by age and sex. METHODS: A population-based sample of 624 participants aged 65-99 years were identified from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) COVID19 Study. Information on pre-pandemic factors was collected through clinical examinations, interviews, and self-administered questionnaires in 2016-2019. Changes in light and intense PA during the first wave of the pandemic (May-September 2020) were self-reported. Data were analyzed using multiple logistic regression models, stratified by age (<70 vs. >80 years) and sex. RESULTS: There was an association between pre-pandemic levels of higher depressive symptom burden (Odds Ratio (OR): 2.6, 95% Confidence Interval (CI): 1.1-6.4, <70 years), and impaired balance (OR: 1.7, 95% CI: 1.0-2.8, >80 years old) with reductions in light-intensity PA. Furthermore, the presence of musculoskeletal disease (OR: 1.8, 95% CI: 1.1-2.9, <70 years; OR: 2.3, 95% CI: 1.2-4.4, men), moderate/high levels of neuroticism (OR: 1.6, 95% CI: 1.0-2.6, <70 years; OR: 2.2, 95% CI: 1.3-3.5, women), and poor levels of social support (OR: 2.2, 95% CI: 1.2-4.3, >80 years) were related to reductions in higher-intensity PA. Those who were current smokers (OR: 0.3, 95% CI: 0.1-0.8, <70 years; OR: 0.2, 95% CI: 0.06-0.7, women), or had impaired balance (OR: 0.4, 95% CI: 0.2-0.8, >80 years) were less likely to reduce their levels of higher-intensity PA. CONCLUSIONS: For future pandemics or waves of COVID-19, development of strategies is warranted for older individuals with psychiatric- or physical illness/dysfunction, as well as those with poor social support to counteract reductions in physical activities.

The Association Between Injurious Falls and Older Adults' Cognitive Function: The Role of Depressive Mood and Physical Performance.

BACKGROUND: The impact of falls on cognitive function is unclear. We explored whether injurious falls are associated with cognitive decline in older adults, and evaluated the role of changes in psychological and physical health as mediators of such association. METHODS: This prospective study involved 2267 community-dwelling participants in the Swedish National study on Aging and Care in Kungsholmen (≥60 years). Data on injurious falls (ie, falls requiring medical attention) during each 3-year time interval of follow-up were obtained from national registers. Assessment of cognitive function (Mini-Mental State Examination), depressive mood (Montgomery-Åsberg Depression Rating Scale), and physical performance (walking speed) were carried out every 3 or 6 years over a 12-year follow-up. The association between falls and cognition was estimated through linear mixed-effects models, and the mediating role of changes in depressive mood and physical performance was tested using mediation analysis. RESULTS: After adjusting for potential confounders, individuals who experienced injurious falls had a greater annual decline in Mini-Mental State Examination in the subsequent time interval (ß = -1.49, 95% CI: -1.84; -1.13), than those who did not. The association increased with the occurrence of ≥2 falls (ß = -2.13, 95% CI: -2.70; -1.56). Worsening of walking speed and depressive mood explained around 26% and 8%, respectively, of the association between falls and cognitive decline. CONCLUSIONS: Injurious falls are associated with greater cognitive decline, and this association is partly mediated by worsening of physical performance and, in a lesser extent, of depressive mood. These findings suggest that physical deficits and low mood are potential therapeutic targets for mitigating the association between falls and cognitive decline.

Fostering healthy aging: The interdependency of infections, immunity and frailty.

Untangling the interdependency of infections, immunity and frailty may help to clarify their roles in the maintenance of health in aging individuals, and the recent COVID-19 pandemic has further highlighted such priority. In this scoping review we aimed to systematically collect the evidence on 1) the impact of common infections such as influenza, pneumonia and varicella zoster on frailty development, and 2) the role played by frailty in the response to immunization of older adults. Findings are discussed under a unifying framework to identify knowledge gaps and outline their clinical and public health implications to foster a healthier aging. Twenty-nine studies (113,863 participants) selected to answer the first question provided a moderately strong evidence of an association between infections and physical as well as cognitive decline - two essential dimensions of frailty. Thirteen studies (34,520 participants) investigating the second aim, showed that frailty was associated with an impaired immune response in older ages, likely due to immunosenescence. However, the paucity of studies, the absence of tools to predict vaccine efficacy, and the lack of studies investigating the efficacy of newer vaccines in presence of frailty, strongly limit the formulation of more personalized immunization strategies for older adults. The current evidence suggests that infections and frailty repeatedly cross each other pathophysiological paths and accelerate the aging process in a vicious circle. Such evidence opens to several considerations. First, the prevention of both conditions pass through a life course approach, which includes several individual and societal aspects. Second, the maintenance of a well-functioning immune system may be accomplished by preventing frailty, and vice versa. Third, increasing the adherence to immunization may delay the onset of frailty and maintain the immune system homeostasis, beyond preventing infections.

Bridging late-life depression and chronic somatic diseases: a network analysis.

The clinical presentation of late-life depression is highly heterogeneous and likely influenced by the co-presence of somatic diseases. Using a network approach, this study aims to explore how depressive symptoms are interconnected with each other, as well as with different measures of somatic disease burden in older adults. We examined cross-sectional data on 2860 individuals aged 60+ from the Swedish National Study on Aging and Care in Kungsholmen, Stockholm. The severity of sixteen depressive symptoms was clinically assessed with the Comprehensive Psychopathological Rating Scale. We combined data from individual clinical assessment and health-registers to construct eight system-specific disease clusters (cardiovascular, neurological, gastrointestinal, metabolic, musculoskeletal, respiratory, sensory, and unclassified), along with a measure of overall somatic burden. The interconnection among depressive symptoms, and with disease clusters was explored through networks based on Spearman partial correlations. Bridge centrality index and network loadings were employed to identify depressive symptoms directly connecting disease clusters and depression. Sadness, pessimism, anxiety, and suicidal thoughts were the most interconnected symptoms of the depression network, while somatic symptoms of depression were less interconnected. In the network integrating depressive symptoms with disease clusters, suicidal thoughts, reduced appetite, and cognitive difficulties constituted the most consistent bridge connections. The same bridge symptoms emerged when considering an overall measure of somatic disease burden. Suicidal thoughts, reduced appetite, and cognitive difficulties may play a key role in the interconnection between late-life depression and somatic diseases. If confirmed in longitudinal studies, these bridging symptoms could constitute potential targets in the prevention of late-life depression.

The complex interplay between depression and multimorbidity in late life: risks and pathways.

Multimorbidity and depression are complex multifactorial conditions with major implications for older individuals, their families, and healthcare providers. In this scoping review, we aimed to 1) review findings from longitudinal epidemiological studies investigating the association between multimorbidity and depression; 2) identify potential mechanisms linking multimorbidity and depression; 3) discuss challenges to advance the research field. Overall, evidence emerging from longitudinal studies supports a bidirectional association between the two conditions, although studies are methodologically heterogeneous in terms of design, inclusion criteria, measurement of multimorbidity and depression, and length of follow-up. A variety of biological, psychosocial, and care-related drivers may regulate the transition from multimorbidity to depression, and the other way around, although these mechanisms are yet to be explicitly verified. Further research is required to unravel the intricate interplay between multimorbidity, depression, their common drivers, and precipitating factors underlying the relationship between the two conditions. Understanding these processes will inform strategies aimed at promoting mental and physical health during aging.

Social engagement in late life may attenuate the burden of depressive symptoms due to financial strain in childhood.

BACKGROUND: It remains poorly understood if childhood financial strain is associated with old-age depression and if active social life may mitigate this relationship. AIMS: To investigate the association between childhood financial strain and depressive symptoms during aging; to examine whether late-life social engagement modifies this association. METHOD: 2884 dementia-free individuals (aged 60+) from the Swedish National study of Aging and Care-Kungsholmen were clinically examined over a 15-year follow-up. Presence of childhood financial strain was ascertained at baseline. Depressive symptoms were repeatedly assessed with the Montgomery-Åsberg Depression Rating Scale. Social engagement comprised information on baseline social network and leisure activities. Linear, logistic and mixed-effect models estimated baseline and longitudinal associations accounting for sociodemographic, clinical, and lifestyle factors. RESULTS: Childhood financial strain was independently associated with a higher baseline level of depressive symptoms (ß = 0.37, 95%CI 0.10-0.65), but not with symptom change over time. Relative to those without financial strain and with active social engagement, depressive burden was increased in those without financial strain but with inactive social engagement (ß = 0.43, 95%CI: 0.15-0.71), and in those with both financial strain and inactive engagement (ß = 0.99, 95%CI: 0.59-1.40). Individuals with financial strain and active social engagement exhibited similar depressive burden as those without financial strain and with active social engagement. LIMITATIONS: Recall bias and reverse causality may affect study results, although sensitivity analyses suggest their limited effect. CONCLUSIONS: Early-life financial strain may be of lasting importance for old-age depressive symptoms. Active social engagement in late-life may mitigate this association.

Instrumental assessment of balance and gait in depression: A systematic review.

Psychomotor symptoms of depression are understudied despite having a severe impact on patient outcomes. This review aims to summarize the evidence on motor features of depression assessed with instrumental procedures, and examine age-related differences. We included studies investigating posture, balance and gait ascertained with instrumental measurements among individuals with depressive symptoms or disorders. Studies on subjects with specific physical illnesses were excluded. Methodological quality was assessed with the Newcastle - Ottawa Scale (NOS) and PRISMA guidelines were followed. 33 studies (13 case-control, five cross-sectional, nine longitudinal and six intervention) with overall low-medium quality were included. Different instruments were employed to assess posture (e.g. digital cameras), balance (balance, stepping platform) or gait (e.g. Six-Minute-Walking Test, instrumented walkways). Results suggest that depression in adults is associated with significant impairments of posture, balance and gait. Motor abnormalities among depressed older adults may depend on the interplay of physical diseases, cognitive impairment and mood. Very few intervention studies measured motor symptoms as outcome. Available evidence suggests, however, that antidepressant drugs and physical exercise may be beneficial for motor abnormalities. Despite the lack of high-quality studies, instrumental assessments confirm the presence and importance of motor abnormalities in depression, with potential age-related differences in their pathophysiology.